Abstract 2809: Knockout of Ca/Calmodulin Kinase II{delta} Protects Against ROS-induced Injury

Expression and activity of Ca/calmodulin kinase II (CaMKII) are enhanced in heart failure (HF) and linked to disease progression involving increased late Na current (INa). Reactive oxygen species (ROS) generated in HF can increase late INa leading to cytosolic Na and Ca overload, arrhythmias and cell death. We tested whether ROS-activated CaMKII δ is involved, since it is known that ROS directly activate CaMKII via oxidation at methionine residues. We exposed ventricular myocytes isolated from CaMKII δ -knockout mice (CKO, wildtype (WT) as control) to ROS generated via 200 μ M H2O2. The H2O2-induced increase of late INa was almost completely abolished in myocytes lacking CaMKII δ (fig 1A). Moreover, in CKO-myocytes the blunted H2O2-induced Na influx via late INa resulted in a significantly slower increase of [Na]i compared to WT (fig 1B, 10 μ M SBFI-AM, ANOVA, *P μ M Indo-1-AM, ANOVA, *P μ M, fig 1C, †P δ is a prerequisite for ROS-induced increase of late INa, [Na]i and [Ca]i accumulation. Moreover, myocytes lacking CaMKII δ are protected from severe arrhythmias and cell death. Therefore, strategies targeted at CaMKII may be promising for the treatment of HF.